Phase 2 Application: 1 R43 GM075509-01 Principle Investigator: Khine, Michelle High Throughput Intracellular Drug Screening Platform Rapid well-controlled intracellular delivery of compounds into a cell - without permanent damage to the cell - is a pervasive challenge in basic cell biology research as well as in drug discovery. The goal for this Phase II project is to continue to further develop a versatile drug-screening bench-top electroporation platform to address this ubiquitous need of academic and bio/pharmaceutical researchers. Our system - developed solely from the Phase 1 grant -- includes a control interface, with disposable 96-well microfluidic chips, that enables cells to each be controlled, monitored and manipulated individually. This platform also enables real-time electrical and optical monitoring of each cell's response. Three important and widely used applications that our system can uniquely address are: (1) drug safety testing via hERG screening (2) integrated transfection of an ion channel construct and ion channel recordings via patch clamp measurements and (3) intracellular delivery of short interfering RNA (siRNA) for target identification and validation. Awardment of this Phase 2 grant would allow us to continue to further develop our single-cell electroporation platform, making intracellular delivery a well-controlled, highly efficient, and parallel process. Phase 2 Application: 1 R43 GM075509-01 Principle Investigator: Khine, Michlle High Throughput Intracellular Drug Screening Platform Project Narrative In the Phase I portion of this grant, we developed a reliable bench-top single-cell microfluidic electroporation platform in a 96-well format. We demonstrated that this system could be used to permeate the cell membranes of an array of suspension cells in a controllable manner. We aim to further develop our platform for its original application as well as for its newfound applications (hERG screening, transfecting/patching, and siRNA delivery) by integrating our platform with electrophysiology capabilities as well as improving its throughput and lowering its required reagent volumes. [unreadable] [unreadable] [unreadable]